Difficulties in the Diagnosis and Management of Paediatric Posterior Circulation Stroke.

We present two children with posterior circulation stroke (PCS) highlighting the wide spectrum of presentation, the need for complete radiological assessment, and the relatively high recurrence risk.

Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies.

A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0·022/patient-year, P < 0·0001); the rate of all infections was 4·38/patient-year. Median trough IgG concentrations were ≥ 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0·101 event/infusion. The incidence of local related AEs was 0·069 event/infusion (0·036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0·032 event/infusion. Most related AEs were mild, none were severe. For 64·6% of patients and in 94·8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0·95 (range = 0·3-4·1) h using mainly one to two administration sites [median = 2 sites (range = 1-5)]. Almost all infusions (99·8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment.

Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010.

In 2011, the Irish Medicines Board received reports of onset of narcolepsy following vaccination against influenza A(H1N1)pdm09 with Pandemrix. A national steering committee was convened to examine the association between narcolepsy and pandemic vaccination. We conducted a retrospective population-based cohort study. Narcolepsy cases with onset from 1 April 2009 to 31 December 2010 were identified through active case finding. Narcolepsy history was gathered from medical records. Pandemic vaccination status was obtained from vaccination databases. Two independent experts classified cases using the Brighton case definition. Date of onset was defined as date of first healthcare contact for narcolepsy symptoms. Incidence of narcolepsy in vaccinated and non-vaccinated individuals was compared. Of 32 narcolepsy cases identified, 28 occurred in children/adolescents and for 24 first healthcare contact was between April 2009 and December 2010. Narcolepsy incidence was 5.7 (95% confidence interval (CI): 3.4­8.9) per 100,000 children/adolescents vaccinated with Pandemrix and 0.4 (95% CI: 0.1­1.0) per 100,000 unvaccinated children/adolescents (relative risk: 13.9; absolute attributable risk: 5.3 cases per 100,000 vaccinated children/adolescents). This study confirms the crude association between Pandemrix vaccination and narcolepsy as observed in Finland and Sweden. The vaccine is no longer in use in Ireland. Further studies are needed to explore the immunogenetic mechanism of narcolepsy.

Spontaneous and field-induced mesomorphism of a silyl-terminated bent-core liquid crystal as determined from second-harmonic generation and resonant X-ray scattering.

The polarity and structure of the phases of a liquid crystal constituted by thiophene-based bent-core molecules is investigated by means of optical second-harmonic generation (SHG), and resonant and conventional X-ray diffraction. The material studied is representative of a wide family of mesogens that contain silyl groups at the ends of the chains. These bulky terminal groups have been reported to give rise to smectic phases showing ferroelectric switching. However, the analysis of the SHG signal before and after application of electric fields has allowed us to establish unambiguously that the reported ferroelectricity is not intrinsic to the material but stabilized by the cell substrates once an electric field has been applied. In addition, the results obtained from resonant X-ray diffraction indicate that virgin samples have antiferroelectric undulated synclinic smectic structures.

Resonant x-ray diffraction study of an unusually large phase coexistence in smectic liquid-crystal films.

The recent discovery of the new smectic-C(d6)(*) (SmC(d6)(*)) phase [S. Wang et al., Phys. Rev. Lett. 104, 027801 (2010)] also revealed the existence of a noisy region in the temperature window between the SmC(d6)(*) phase and the smectic-C(d4)(*) (SmC(d4)(*)) phase. Characterized by multiple resonant peaks spanning a wide region in Q(Z), the corresponding structure of this temperature window has been a mystery. In this Letter, through a careful resonant x-ray diffraction study and simulations of the diffraction spectra, we show that this region is in fact an unusually large coexistence region of the SmC(d6)(*) phase and the SmC(d4)(*) phase. The structure of the noisy region is found to be a heterogeneous mixture of local SmC(d6)(*) and SmC(d4)(*) orders on the sub-µm scale.

Effect of enantiomeric excess on the phase behavior of antiferroelectric liquid crystals.

Null transmission ellipsometry and resonant x-ray diffraction are employed to study the effect of enantiomeric excess (EE) on the phase behavior of antiferroelectric liquid crystal 10OTBBB1M7. Phase sequence, layer spacing, and pitch of the helical structures of the smectic-C(α)* and smectic-C* phases are studied as a function of temperature and EE. Upon reducing EE, a liquid-gas-type critical point of the smectic-C(α)* to smectic-C* transition is observed, as well as the disappearance of the smectic-C(d4)* and the smectic-C(d3)* phases. Results are analyzed in a mean-field model.

Surface and bulk uniaxial to biaxial smectic-A transition in a bent core liquid crystal.

A null transmission ellipsometer was employed to study the uniaxial to biaxial smectic-A phase transition of a bent core liquid crystal material. Free-standing films of thicknesses ranging from 5 molecular layers to more than 300 were prepared and studied. Critical exponents for both the surface and interior biaxiality were obtained. The results were discussed in the general framework of phase transition in lower dimensions.

Evolution of a rare sequence of surface transitions with temperature and film thickness.

In free-standing smectic films, layers near the surfaces of the film often contain molecules tilted away from the layer normal, while in the bulk of the film the magnitude of the tilt decays exponentially with distance from the surface. We have identified the detailed molecular tilt orientations in the surface layers of films for one antiferroelectric liquid crystal compound. A series of five surface structures exists with different nonplanar tilt arrangements for each structure. The molecular orientations in the surface layers evolve with temperature. The polarization of the film also evolves with temperature, corresponding to the tilt arrangements. Using ellipsometric data, we reconstruct the changes in the magnitude and azimuthal direction of the tilt as functions of temperature. We have also studied films of several different thicknesses. We present a phase diagram for the five surface structures showing the dependence on temperature and film thickness.

Nonplanar tilts in very thin smectic films of one liquid-crystal compound.

Surface effects cause tilted molecular arrangements in smectic layers near the surface of a free-standing liquid-crystal film in which the bulk of the film is in the smectic- A phase. One recent work has shown that the tilt directions in adjacent surface layers may be nonplanar. In this paper we study films with thicknesses of two to six smectic layers. Surface effects dominate in these very thin films. We show that the molecular tilts are nonplanar even in these very thin films.

Recovery of a reversed phase sequence in one ternary liquid-crystal-mixture system.

The nOHFBBB1M7 (n=10) compound, 10OHF, shows a reversed SmC{FI2}-SmC phase sequence, unique among all known antiferroelectric liquid crystals. This reversed phase sequence is stabilized when 10OHF is doped with 9OTBBB1M7(C9) or 11OTBBB1M7(C11). In contrast, doping of the homologous members ( n=9 , 11, or 12) eliminates the SmC{FI2} phase. One 10OHF/11OHF mixture without the SmC{FI2} phase was selected for further studies. By adding C9 into this particular mixture, the reversed phase sequence is revived. To our surprise, even though 11OHF destabilizes the SmC_{FI2} phase in binary mixtures with 10OHF, it significantly increases the SmC_{FI2} temperature range in the 10OHF/11OHF/C9 ternary mixtures.

Sensory-motor polyneuropathy occurring in variant maple syrup urine disease.

Maple syrup urine disease (MSUD; OMIM 248600) results from an inherited deficiency of the branched-chain ketoacid dehydrogenase (BCKD) complex. Approximately 20% of patients with BCKD deficiency are non-classic variants of MSUD with differing clinical severity. Outcomes for this cohort are generally favourable; episodes of metabolic decompensation do not appear to correlate with adverse events if acute management is promptly provided. A case of predominantly axonal sensory-motor neuropathy following metabolic decompensation which persisted for a number of months is presented in an adolescent girl with variant (intermediate type) MSUD. EMG and nerve conduction studies suggested a pre-existent asymptomatic chronic neuropathy, exacerbated by the acute decompensation. Peak leucine concentration at decompensation was 1083 µmol/L. The patient had laboratory signs of secondary mitochondrial respiratory chain dysfunction at presentation. She had been on a moderate dose of thiamine prior to decompensation; thiamine and pyridoxine blood concentrations were normal. This, to our knowledge, is the first report of a neuropathy presenting in a patient with a decompensation of variant MSUD. We propose that this presentation resembles the intermittent neuropathy observed in pyruvate dehydrogenase deficiency and may reflect secondary inhibition of pyruvate dehydrogenase activity by MSUD metabolites.

Effects of doping on an unusual smectic- C*alpha-smectic-C*FI2-smectic-C* phase sequence.

The compound 10OHF has a partially inverted phase sequence, unique among the series of nOHF homologous compounds and all other known liquid crystals, with the smectic-C*FI2 (SmC*FI2) phase occurring at higher temperature than the smectic-C* (SmC*) phase. We present ellipsometric data to identify the phase sequences of 9OHF, 10OHF, 11OHF, and 12OHF. Binary mixtures of 10OHF with C11, a compound with the typical phase sequence among the smectic phases, show that the unusual phase sequence of 10OHF stabilizes upon mixing and that SmC*FI2 predominates over SmC* throughout the entire mixing phase diagram. In thin films of some mixtures, surface interactions induce a reentrant SmC*FI2-SmC*-SmC*FI2 transition in the rest of the film.

Unique pitch evolution in the smectic-C+alpha phase.

Employing resonant x-ray diffraction, we observed unique pitch evolutions in the smectic-C*(alpha) phase in mixtures of two antiferroelectric liquid crystals. Our results show that the pitch in this phase continuously evolves across 4 layers, contradicting a theoretical model that predicts that the smectic-C*(FI2) phase intervenes in the smectic-C*(alpha) phase. The phase sequences we found can be explained by another model that includes one type of long-range interaction among smectic layers.

Smectic-C*alpha phase with two coexistent helical pitch values and a first-order smectic-C*alpha to smectic-C* transition.

Previous results from Kundu using dielectric relaxation have suggested a reentrant antiferroelectric-ferroelectric-antiferroelectric transition in the compound LN36. Our comprehensive studies of this compound using differential optical reflectivity, nonadiabatic scanning calorimetry, null transmission ellipsometry, and resonant x-ray diffraction show that in fact LN36 exhibits the usual phase sequence for chiral smectic liquid crystals: SmA*-SmC*alpha-SmC*-SmC*FI1-SmC*A . Moreover, the SmC*alpha-SmC* transition is a first-order transition, characterized by a discontinuous change in the helical pitch. At temperatures just above the SmC*alpha-SmC* transition, two different values for the helical pitch are simultaneously observed for the first time.

Polarization studies of resonant forbidden reflections in liquid crystals.

We report the results of resonant x-ray diffraction experiments performed on thick films of a biaxial liquid crystal made of achiral bent-core molecules. Polarization properties of forbidden reflections are observed as a function of the sample rotation angle phi about the scattering vector Q for the first time on a fluid material. The experimental data are successfully analyzed within a tensor structure factor model by taking the nonperfect alignment of the liquid crystal into account. The local structure of the B2 mesophase is hence determined to be SmC_{S}P_{A}.

Smectic-Calpha*-smectic-C* phase transition and critical point in binary mixtures.

We have investigated the smectic-Calpha*-smectic-C* (SmCalpha*-SmC*) transition in a series of binary mixtures with resonant x-ray diffraction, differential optical reflectivity, and heat capacity measurements. Results show that the phases are separated by a first-order transition that ends at a critical point. We report the observation of such a critical point. We have proposed the appropriate order parameter and obtained values of two critical exponents associated with this transition. The values of the critical exponents suggest that long-range interactions are present in the SmCalpha*-SmC* critical region.

Optical studies on the surface-induced tilted layers in freestanding films of two no-layer-shrinkage liquid crystal compounds.

Null transmission ellipsometry has been employed to study the molecular arrangements in freestanding films of two no-layer-shrinkage liquid crystal homologous compounds above the bulk smectic A-smectic C* (Sm C*) transition temperature. An unusual nonplanar-parallel or nonplanar-antiparallel-parallel transition has been observed in both compounds under a proper electric field. With the addition of one CH2 group, while the SmC* phase is more stable thermally, the magnitude of the critical field needed to induce a parallel-antiparallel transition decreases dramatically.

Investigations of nanoscale helical pitch in smectic-C*alpha and smectic-C* phases of a chiral smectic liquid crystal using differential optical reflectivity measurements.

Differential optical reflectivity (DOR) was used to study the temperature dependence of the short helical pitch in freestanding films of a liquid crystal compound. The experimentally measured DOR signal was fitted using Berreman's 4 x 4 matrix method to get the pitch value in the smectic-C*alpha (sMC*alpha) phase. The results show continuous evolution of the pitch between the smectic-C*alpha and sMC*alpha phases. In sMC*alpha, the pitch decreases as temperature increases and is found to level off at 16+/-1 smectic layers at the sMC*alpha to smectic-A* transition.

Surface-induced multiple reentrant transitions.

We have studied tilted surface layers in the bulk SmA temperature window of one liquid crystal using null transmission ellipsometry. Five distinct nonplanar surface structures were observed. We present analyses of the tilt and azimuthal profiles of the structures and examine the transitions between the structures. The transitions are identified as a double reentrant synclinic-anticlinic-synclinic-anticlinic transition. Meanwhile, the transitions also display reentrant ferroelectric-antiferroelectric-ferroelectric behavior.